Original Article
Determinants of White Matter Hyperintensity Burden Differ at the Extremes of Ages of Ischemic Stroke Onset

https://doi.org/10.1016/j.jstrokecerebrovasdis.2014.10.016Get rights and content

Background

Age is a well-known risk factor for both stroke and increased burden of white matter hyperintensity (WMH), as detected on magnetic resonance imaging (MRI) scans. However, in patients diagnosed with ischemic stroke (IS), WMH volume (WMHv) varies significantly across age groups. We sought to examine the determinants of WMH burden across the ages of stroke onset with the goal to uncover potential age-specific stroke prevention targets.

Methods

Adult subjects from an ongoing hospital-based cohort study of IS patients with admission brain MRI were categorized as having early (<55 years), late (>75 years), or average (55-75 years) age of stroke onset. WMHv was measured using a previously validated, MRI-based semi-automated method and normalized for linear regression analyses.

Results

Of 1008 IS subjects, 249 had early-onset stroke (24.7%), and 311 had late-onset stroke (30.9%). In multivariable analysis of WMHv using backward stepwise selection, only age (β = .02, P = .018), hypertension (β = .24, P = .049), and history of tobacco use (β = .38, P = .001) were independently associated with WMHv in patients with early-onset stroke, whereas male sex (β = −.30, P = .007), hyperlipidemia (β = −.27, P = .015), and current alcohol use (β = .23, P = .034) were independently associated with WMHv in patients with late-onset stroke.

Conclusions

History of tobacco use is a strong independent predictor of WMH burden in patients with early-onset stroke, whereas age is no longer associated with WMHv in IS patients older than 75 years of age. These findings suggest that the major risk factors to target for stroke prevention differ across age groups and may be modifiable.

Section snippets

Patient Selection and Definitions

Study subjects were recruited as part of an ongoing hospital-based study of patients with ischemic stroke (IS).17 Consecutive patients aged 18 years of age or older admitted to the Massachusetts General Hospital Stroke Unit, including those admitted directly to the emergency department or transferred to the emergency department from a referring hospital, between July 2000 and December 2013 were considered for enrollment. Patients underwent clinical evaluation by a neurologist and diagnostic

Results

The mean age of 1008 consenting subjects with IS was 65.9 (±14.7) years of age; there were 249 (24.7%) PEOS, 448 (44.4%) PAAOS, and 311 (30.9%) PLOS (Table 1). Males represented 61.7% of the cohort. Median adjusted WMHv for all subjects was 6.0 cm3 (interquartile range, 2.7-12.5 cm3) and mean normalized WMHv was 1.8 (±1.1). WMHv and prevalence of AF, CAD, and history of TIA increased with age of stroke onset. A majority of subjects had HTN, except within the PEOS population (39.4%), which also

Discussion

In this analysis, we report that the determinants of WMH burden differ with age of stroke onset. Notably, history of tobacco use is an independent predictor of WMH severity specific to the youngest IS patients (PEOS), whereas age loses its effect as a determinant of WMHv in the elderly (PLOS). The importance of these novel data is that they are derived from the largest-to-date, hospital-based cohort of IS subjects with WMH severity quantified on brain MRI using a volumetric method and that they

Summary

In this cohort, history of tobacco use is a strong independent predictor of WMH burden in patients who experience IS before the age of 55 years, whereas female sex, HL, and current alcohol use, but not age, independently contribute to severity of WMH in those with stroke onset after 75 years of age. These findings suggest that the major risk factors for WMH and stroke differ across age groups and are modifiable. Future studies that target age-specific prevention strategies of symptomatic

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  • Cited by (0)

    This study was supported by project grants from the American Heart Association Bugher Foundation, the Deane Institute for Integrative Research in Atrial Fibrillation and Stroke, Massachusetts General Hospital, and the National Institute of Neurological Disorders and Stroke (NINDS grants K23 NS064052 and R01 NS082285). C.R.Z., L.C., K.F., A.K., and A.M.A. report no disclosures. K.L.F. is supported by the NINDS (5P50NS051343-04). J.R. is supported by the NINDS (5R01NS059727, 5P50NS051343, R01NS063925) and the American Heart Association Bugher Foundation. N.S.R. is supported by the NINDS (K23NS064052 and R01NS082285).

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